Contemporary clinical effects of phytoestrogens administration

Milan Terzic, Jelena Dotlic

Research output: Chapter in Book/Report/Conference proceedingChapter


Phytoestrogens are natural polycyclic phenols found in certain plants that are structurally and functionally similar to 17ß-estradiol. When ingested and metabolized, they bind to estrogen receptors (mainly estradiol ß2 receptors - ER ß2) and produce estrogenic effects. Furthermore, they also bind to peroxisome proliferator-activated receptor (PPAR) family and aryl hydrocarbon receptors. Moreover, phytoestrogens affect activity of tyrosine kinases, histones, transcription factors, AMP (Adenosine mono phosphate) pathways, RNA expression and other intracellular regulators. Current research demonstrates that phytoestrogens are helpful in reducing the intensity and frequency of hot flushes in menopausal women. Still, complete elimination cannot be achieved, as phytoestrogens have weaker biological activity than endogenous and synthetic estrogens. Certain phytoestrogens have also been shown to decrease vaginal atrophy. Moreover, unlike hormone therapy, phytoestrogens were not found to increase clotting risk. Studies confirmed beneficial effects of phytoestrogens on endothelial cells, vascular smooth muscle and extracellular matrix cells. Due to nitrogen oxide (NO) production they decrease arterial stiffness and exert anti-atherosclerotic effects. Phytoestrogens also affect angiogenesis and reduce inflammation and tissue damage, which delays the progression of atherosclerosis. Furthermore, phytoestrogens increase high density lipoprotein (HDL) and decrease low density lipoprotein (LDL) concentrations in human plasma. Neuroprotective effects of phytoestrogens are related to both their antioxidant properties and interaction with ER. Literature data show that phytoestrogens might improve cognition, prevent or at least postpone dementia. By activating PPARγ receptors phytoestrogens down-regulate pro-inflammatory cytokines, such as Cyclooxygenase 2 (COX-2) and Inducible nitric oxide synthase (iNOS), increase reverse cholesterol transport and insulin sensitivity. Phytoestrogens increase energy expenditure by affecting AMP activated kinase signaling cascades, which inhibit adipogenesis. Therefore, they can exert different effects on metabolism and may complement conventional treatment for diseases linked to metabolic syndrome, polycystic ovary syndrome and diseases related to hyper-androgenism and obesity. Phytoestrogens have shown antiresorptive effects on bone through ER signaling. Additionally, they also affect broad spectrum of molecular mechanisms supporting osteogenesis by inhibiting PPARγ, Sirtuin 1 and CCAAT-enhancer-binding proteins (C/EBP) α, the key adipogenic transcription factors. Stimulating main osteogenic transcription factors Core-binding factor subunit alpha-1 (CBF-alpha-1) and Osterix, they present themselves as a new strategy for treating bone loss. Literature data strongly support the relationship between phytoestrogen diet supplementation and the lower risk for some cancers. Phytoestrogens have been shown to inhibit the carcinogenesis through the modulation of genes that control the cell-cycle progression. They inhibit the activation of the nuclear transcription factor, kappa light polypeptide gene enhancer in B-cells (NF-kappa B) and protein kinase B signaling pathway, which are known to maintain a homeostatic balance between cell survival and programmed cell death (apoptosis). Phytoestrogens are also implicated in reversion of epigenetic events observed in some cancers. Furthermore, phytoestrogens are known to have potent antioxidant properties (inhibition of oxidative stress) and are found to be potent inhibitors of angiogenesis and metastasis. Moreover, phytoestrogens regulate mucosal immune response by suppressing dendritic cell function. In conclusion, phytoestrogens appear to exert numerous positive health effects and consequently are recommended for use in various clinical fields.

Original languageEnglish
Title of host publicationGenistein and Daidzein
Subtitle of host publicationFood Sources, Biological Activity and Health Benefits
PublisherNova Science Publishers, Inc.
Number of pages22
ISBN (Electronic)9781634832168
ISBN (Print)9781634831949
Publication statusPublished - Jan 1 2015
Externally publishedYes


  • Bone
  • Cancer
  • Cardiovascular system
  • Cognition
  • Hot flushes
  • Metabolic syndrome
  • Phytoestrogens

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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